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Viruses Apr 2023Dengue has been one of the major public health concerns in the Philippines for more than a century. The annual dengue case burden has been increasing in recent years,...
Dengue has been one of the major public health concerns in the Philippines for more than a century. The annual dengue case burden has been increasing in recent years, exceeding 200,000 in 2015 and 2019. However, there is limited information on the molecular epidemiology of dengue in the Philippines. We, therefore, conducted a study to understand the genetic composition and dispersal of DENV in the Philippines from 2015 to 2017 under UNITEDengue. Our analyses included 377 envelope () gene sequences of all 4 serotypes obtained from infections in 3 main island groups (Luzon, Visayas, and Mindanao) of the Philippines. The findings showed that the overall diversity of DENV was generally low. DENV-1 was relatively more diverse than the other serotypes. Virus dispersal was evident among the three main island groups, but each island group demonstrated a distinct genotype composition. These observations suggested that the intensity of virus dispersal was not substantive enough to maintain a uniform heterogeneity among island groups so that each island group behaved as an independent epidemiological unit. The analyses suggested Luzon as one of the major sources of DENV emergence and CAR, Calabarzon, and CARAGA as important hubs of virus dispersal in the Philippines. Our findings highlight the importance of virus surveillance and molecular epidemiological analyses to gain deep insights into virus diversity, lineage dominance, and dispersal patterns that could assist in understanding the epidemiology and transmission risk of dengue in endemic regions.
Topics: Humans; Dengue Virus; Dengue; Phylogeny; Philippines; Genotype; Genetic Variation
PubMed: 37243165
DOI: 10.3390/v15051079 -
Journal of Infection in Developing... Oct 2022Dengue is an emerging vector-borne public health threat and characterization at the molecular level is important for proper management of the disease. The aim of the...
INTRODUCTION
Dengue is an emerging vector-borne public health threat and characterization at the molecular level is important for proper management of the disease. The aim of the study is to examine the diversity of the dengue viral serotypes from a hilly mountainous region of Northeast India.
METHODOLOGY
Thirty-six blood samples that were positive for dengue virus IgM antibodies identified by the enzyme-linked immunosorbent assay (ELISA) method were collected and quantified for the IL6 gene expression by using reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTS
All the patients had dengue hemorrhagic fever (DHF); 12 samples had a monotypic infection and 14 samples had dual infection with various dengue virus (DENV) serotypes; one sample had triple infection with DENV-1, DENV-2, and DENV-3.
CONCLUSIONS
This study identified DENV-1 as the major serotype in the state of Mizoram and it is the first report on the molecular typing of the dengue virus from the hilly mountainous state located in the Indo-Burma region bordering Myanmar and Bangladesh.
Topics: Humans; Dengue Virus; Dengue; Serogroup; Enzyme-Linked Immunosorbent Assay; Molecular Typing; India; Antibodies, Viral
PubMed: 36332218
DOI: 10.3855/jidc.16137 -
Viruses Feb 2020Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection...
Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5' UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.
Topics: Cell Line; Cells, Cultured; Dengue; Dengue Virus; Dermis; Fibroblasts; Hair Follicle; Host-Pathogen Interactions; Humans; Viral Plaque Assay; Virus Replication
PubMed: 32121148
DOI: 10.3390/v12030267 -
Current Opinion in Virology Aug 2020
Topics: Animals; Culicidae; Dengue; Dengue Virus; Humans; Seasons
PubMed: 33160602
DOI: 10.1016/j.coviro.2020.10.004 -
Frontiers in Cellular and Infection... 2021Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb RNA genome of the dengue virus encodes three structural proteins... (Review)
Review
Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb RNA genome of the dengue virus encodes three structural proteins (envelope, pre-membrane, capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), all of which are translated as a single polyprotein that is subsequently cleaved by viral and host cellular proteases at specific sites. Non-structural protein 5 (NS5) is the largest of the non-structural proteins, functioning as both an RNA-dependent RNA polymerase (RdRp) that replicates the viral RNA and an RNA methyltransferase enzyme (MTase) that protects the viral genome by RNA capping, facilitating polyprotein translation. Within the human host, NS5 interacts with several proteins such as those in the JAK-STAT pathway, thereby interfering with anti-viral interferon signalling. This mini-review presents annotated, consolidated lists of known and potential NS5 interactors in the human host as determined by experimental and computational approaches respectively. The most significant protein interactors and the biological pathways they participate in are also highlighted and their implications discussed, along with the specific serotype of dengue virus as appropriate. This information can potentially stimulate and inform further research efforts towards providing an integrative understanding of the mechanisms by which NS5 manipulates the human-virus interface in general and the innate and adaptive immune responses in particular.
Topics: Animals; Dengue Virus; Host-Pathogen Interactions; Humans; RNA, Viral; RNA-Dependent RNA Polymerase; Viral Nonstructural Proteins
PubMed: 33816326
DOI: 10.3389/fcimb.2021.574067 -
Emerging Microbes & Infections Dec 2022Dengue is caused by four genetically distinct viral serotypes, dengue virus (DENV) 1-4. Following transmission by mosquitoes, DENV can cause a broad spectrum of...
Dengue is caused by four genetically distinct viral serotypes, dengue virus (DENV) 1-4. Following transmission by mosquitoes, DENV can cause a broad spectrum of clinically apparent disease ranging from febrile illness to dengue hemorrhagic fever and dengue shock syndrome. Progress in the understanding of different dengue serotypes and their impacts on specific host-virus interactions has been hampered by the scarcity of tools that adequately reflect their antigenic and genetic diversity. To bridge this gap, we created and characterized infectious clones of DENV1-4 originating from South America, Africa, and Southeast Asia. Analysis of whole viral genome sequences of five DENV isolates from each of the four serotypes confirmed their broad genetic and antigenic diversity. Using a modified circular polymerase extension reaction (CPER), we generated viruses from these isolates. The resultant clones replicated robustly in human and insect cells at levels similar to those of the parental strains. To investigate properties of these genetically diverse isolates, representative viruses from each DENV serotype were administered to NOD Rag1, IL2rg Flk2 (NRGF) mice, engrafted with components of a human immune system. All DENV strains tested resulted in viremia in humanized mice and induced cellular and IgM immune responses. Collectively, we describe here a workflow for rapidly generating infectious clones of DENV - and conceivably other RNA viruses. The infectious clones described here are a valuable resource for reverse genetic studies and for characterizing host responses to DENV and .
Topics: Aedes; Animals; Antibodies, Viral; Antigenic Variation; Dengue; Dengue Virus; Genetic Variation; Humans; Immunoglobulin M; Mice; Mice, Knockout; Reverse Genetics; Serogroup
PubMed: 34931940
DOI: 10.1080/22221751.2021.2021808 -
Communicable Diseases Intelligence... Jun 2021To describe an autochthonous dengue virus type 2 (DENV-2) outbreak in Central Queensland from May 2019 and subsequent public health actions.
OBJECTIVE(S)
To describe an autochthonous dengue virus type 2 (DENV-2) outbreak in Central Queensland from May 2019 and subsequent public health actions.
DESIGN AND SETTING
Public health outbreak investigation of locally acquired DENV-2 cases in Rockhampton, Central Queensland. This included laboratory investigations, associated mosquito vector surveillance, and control measures implemented in response to the outbreak.
RESULTS
Twenty-one locally-acquired DENV-2 cases were identified during the Rockhampton outbreak (from 23 May to 7 October 2019): 13 laboratory-confirmed and eight probable cases. Clinical symptoms included lethargy (100%); fever (95%); headache (95%); and aches and pains (90%). Inspections of premises demonstrated that Aedes aegypti was present in 9.5% of those investigated which was more than half of the premises identified as containing mosquitoes. Nucleotide sequencing of a DENV-2 isolate recovered from the first confirmed case and DENV-2 RNA from an additional 5 patients indicated a single DENV-2 strain was responsible for the outbreak which was most closely related to DENV-2 strains from Southeast Asia.
CONCLUSIONS
The 2019 DENV-2 outbreak in Rockhampton, Central Queensland, Australia, likely resulted from the importation of a strain, most closely related to DENV-2 strains from Southeast Asia and is the first reported outbreak in the region specifically implicating DENV-2. Given the presence of Aedes aegypti in Rockhampton, appropriate medical and mosquito avoidance advice; ongoing surveillance; and deployment of mosquito control strategies for the prevention of dengue and other mosquito-borne diseases should be priorities for this region.
Topics: Animals; Australia; Dengue; Dengue Virus; Disease Outbreaks; Humans; Queensland
PubMed: 34139967
DOI: 10.33321/cdi.2021.45.31 -
Communications Biology May 2021Dengue virus (DENV) is spread from human to human through the bite of the female Aedes aegypti mosquito and leads to about 100 million clinical infections yearly....
Dengue virus (DENV) is spread from human to human through the bite of the female Aedes aegypti mosquito and leads to about 100 million clinical infections yearly. Treatment options and vaccine availability for DENV are limited. Defective interfering particles (DIPs) are considered a promising antiviral approach but infectious virus contamination has limited their development. Here, a DENV-derived DIP production cell line was developed that continuously produced DENV-free DIPs. The DIPs contained and could deliver to cells a DENV serotype 2 subgenomic defective-interfering RNA, which was originally discovered in DENV infected patients. The DIPs released into cell culture supernatant were purified and could potently inhibit replication of all DENV serotypes in cells. Antiviral therapeutics are limited for many viral infection. The DIP system described could be re-purposed to make antiviral DIPs for many other RNA viruses such as SARS-CoV-2, yellow fever, West Nile and Zika viruses.
Topics: Animals; Cell Line, Tumor; Chlorocebus aethiops; Defective Viruses; Dengue; Dengue Vaccines; Dengue Virus; Genes, Reporter; HEK293 Cells; Host-Pathogen Interactions; Humans; Luminescent Proteins; RNA, Viral; Vero Cells; Viral Load; Virus Replication
PubMed: 33976375
DOI: 10.1038/s42003-021-02064-7 -
Microbiology Spectrum Oct 2022Endoplasmic reticulum (ER)-shaping atlastin proteins (ATLs) have been demonstrated to play a functional role during flavivirus replication in mammalian cells. For dengue...
Endoplasmic reticulum (ER)-shaping atlastin proteins (ATLs) have been demonstrated to play a functional role during flavivirus replication in mammalian cells. For dengue virus (DENV), atlastin is required in the formation of the replication organelles and RNA replication, virion assembly, production of the infectious virus particles, and trafficking or directing the association of vesicle packets with furin. Here, we investigated the involvement of atlastin in DENV replication in the mosquito Aedes aegypti and explored the possibility of its manipulation by the endosymbiotic bacterium to interfere with DENV replication. Results showed the expression of gene (AaATL) was upregulated in DENV-infected Aag2 cells, and its silencing led to reduced DENV replication. Contrary to our assumption that AaATL could be downregulated by , we did not find evidence for that in -infected cell lines, but this was the case in mosquitoes. Further, silencing AaATL did not have any effect on density. Our results also suggest that aae-miR-989 miRNA negatively regulates AaATL. The oversupply of the miRNA mimic led to reduced DENV replication consistent with the positive role of AaATL in DENV replication. Overall, the results favor AaATL's involvement in DENV replication; however, there is no support that the protein is involved in -mediated DENV inhibition. In addition, the results contribute to discerning further possible overlapping functions of ATLs in mosquitoes and mammalian cells. Atlastin is a protein associated with the endoplasmic reticulum and has been shown to play a role in replication of flaviviruses in mammalian cells. This study aimed to investigate the role of mosquito Aedes aegypti atlastin (AaATL) in dengue virus replication and maintenance of , an endosymbiotic bacterium, in the mosquito. Our results suggest that AaATL facilitates dengue virus replication in mosquito cells, considering silencing the gene led to reductions in virus replication and virion production. Further, AaATL was found to be regulated by a mosquito microRNA, aae-miR-989. Despite an effect on dengue virus, AaATL silencing did not affect replication and maintenance in mosquito cells. The results shed light on the role of atlastins in mosquito-pathogen interactions and their overlapping roles in mosquito and mammalian cells.
Topics: Animals; Aedes; Dengue; Dengue Virus; Furin; MicroRNAs; Virus Replication; Wolbachia
PubMed: 36165808
DOI: 10.1128/spectrum.02258-22 -
Frontiers in Cellular and Infection... 2022Mosquito-borne diseases are still threats to public health in the Zhejiang province of China. Surveillance of mosquitoes and the mosquito-borne pathogen is a vital...
Mosquito-borne diseases are still threats to public health in the Zhejiang province of China. Surveillance of mosquitoes and the mosquito-borne pathogen is a vital approach for early warning, prevention, and control of the infectious disease. In this study, from 2018 to 2020, a total of 141607 female mosquitoes were caught by means of the light trap method. The main species were (41.32%), (47.6%), (2.5%), (5.87%), (2.64%) and other mosquito species (0.07%). were the dominant species in two urban habitats and rural residential areas while was the main dominant species in the rural livestock sheds. In terms of seasonal fluctuation, Cx. pipiens s.l fluctuated at a high level from May to October. The peaks of Cx. tritaeniorhynchus, An. sinensis and Ar. subalbatus were in July. In addition, a total of 693 were collected with Biogents Mosquitaire CO traps in emergency surveillance of dengue fever (DF) and screened for dengue virus infection. There were three circumstances of collection: The first: the sampling time before mosquito control during the local outbreak of DF in Lucheng of Wenzhou, 2019; The second circumstance: the sampling time after mosquito control during the local outbreak of DF of other cities in 2018-2019; The third circumstance: past DF epidemic areas the sampling time before mosquito control during the local outbreak of DF in Lucheng, Wenzhou, Zhejiang, 2019. The pools formed by mosquitoes collected in these three circumstances were 3 (6.1%), 35 (71.5%), and 11 (22.4%) respectively. Of the 49 pools tested, only one in the first circumstance was positive. The full-length dengue virus sequence of ZJWZ/2019 was obtained by sequencing and uploaded to the NCBI as number OK448162. Full-length nucleotide and amino acid homology analyses showed that ZJWZ2019 and Wenzhou DF serum isolates ZJWZ-62/2019 (MW582816) and ZJWZ-18/2019 (MW582815) had the highest homology. The analysis of full genome and E gene phylogenetic trees showed that ZJWZ2019 belonged to serotype 1, genotype I, lineage II, which was evolutionarily related to OK159963/Cambodia/2019. It implies that ZJWZ2019 originated in Cambodia. This study showed the species composition, seasonal dynamics of mosquitoes in different habitats in Zhejiang province and confirmed the role of in the transmission cycle of in outbreak of DF in the Lucheng district of Wenzhou in 2019, suggesting the importance of monitoring of vector infected dengue virus in the prevention and control of DF.
Topics: Aedes; Animals; China; Culex; Dengue Virus; Disease Outbreaks; Female; Mosquito Vectors; Phylogeny
PubMed: 35846756
DOI: 10.3389/fcimb.2022.834766